Hair follicle stem cell differentiation is inhibited through cross-talk between Wnt/β-catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia
Background Hair follicle (HF) regeneration begins when signals from the mesenchyme-derived dermal papilla cells (DPC) reach multipotent epidermal stem cells in the bulge region. Wnt/β-catenin signalling is known to affect mammalian hair growth positively. In androgenetic alopecia (AGA), androgens ca...
| Authors: | , , |
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| Format: | article |
| Status: | Published version |
| Publication Date: | 2012 |
| Country: | Argentina |
| Institution: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repository: | CONICET Digital (CONICET) |
| Language: | English |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/67895 |
| Online Access: | http://hdl.handle.net/11336/67895 |
| Access Level: | Open access |
| Keyword: | Dermal Papilla Hair Follicle Stem Cells Androgens Wnt/ Beta Catenin Signalling Pathway https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| Summary: | Background Hair follicle (HF) regeneration begins when signals from the mesenchyme-derived dermal papilla cells (DPC) reach multipotent epidermal stem cells in the bulge region. Wnt/β-catenin signalling is known to affect mammalian hair growth positively. In androgenetic alopecia (AGA), androgens cause HF miniaturization through a mechanism that remains unclear. Circulating androgens act on DPC and alter paracrine factors that influence hair epithelial cells. Objectives To elucidate the role of androgens in dermal papilla-induced differentiation of HF stem cells. Methods HF stem cell differentiation was evaluated in a coculture model with DPC or culturing with media conditioned by DPC after activation of androgen and Wnt/β-catenin signalling pathways. To study the molecular cross-talk between the androgen and Wnt signalling pathway in DPC, we analysed the expression and activation of downstream Wnt signalling molecules in the presence of androgens. Results In a coculture model with human DPC from patients with AGA and HF stem cells, we observed that androgens abrogate hair differentiation evaluated by hair-specific keratin 6 expression. Wnt signalling activation restored the ability of androgen-treated DPC to induce differentiation. Androgen treatment revealed a significant decrease in the cytoplasmic/total β-catenin protein ratio and upregulation of the activity of glycogen synthase kinase-3β in DPC, indicative of canonical Wnt pathway inhibition. Conclusions These results suggest that androgens deregulate DPC-secreted factors involved in normal HF stem cell differentiation via the inhibition of the canonical Wnt signalling pathway. © 2012 The Authors. BJD © 2012 British Association of Dermatologists. |
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